title: Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies.
abstract: We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100-110 mg/m(2)) myeloablative conditioning in 48 patients with nonremission AML (n = 14), ALL (n = 10), NHL (n = 18), and other refractory hematologic malignancies (n = 6) who received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a mismatch donor. All patients received tacrolimus with or without methotrexate for GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and disease free. Engraftment was complete in all patients. The median time to ANC recovery (>500) was 12 days (range, 6-28). The most common grade III and IV toxicities were mucositis and infections. Eighteen patients (43 %) developed grade II-IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44 evaluable patients for response, 28 (64 %) achieved a complete remission (CR), and seven (15 %) had a partial remission after the transplant. With a median follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative incidence of relapse was 45 % at 1 year, and the probability of overall survival (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count (<80,000/mL) and lactic dehydrogenase (>500 IU/L) at SCT were associated with relapse. Age less than 53 years and CR after SCT were associated with better OS. Our data suggest that TBI-MEL can result in CR in two thirds, durable remission in one third, and 5-year survival in about one quarter of patients with nonremission hematologic malignancies. Further studies with TBI-MEL in standard risk transplant patients are warranted.
authors.affiliation: Blood and Marrow Transplantation Program, The Marlene and Stewart Greenebaum Cancer Center, Department of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Bhatnagar
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Rapoport
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Fang
authors.forename: Can
authors.initials: C
authors.lastname: Ilyas
authors.forename: Deniz
authors.initials: D
authors.lastname: Marangoz
authors.forename: Vinil
authors.initials: V
authors.lastname: Akbulut
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ruehle
authors.forename: Ashraf
authors.initials: A
authors.lastname: Badros
authors.forename: Saul
authors.initials: S
authors.lastname: Yanovich
authors.forename: Görgün
authors.initials: G
authors.lastname: Akpek
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation / Q000379:methods; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan